The goal of this project is to elucidate basic principles of olfactory system function and organization. In particular, it seeks to explain the logic by which odors are encoded and the molecular organization of the system that encodes them. The experimental plan takes advantage of the fruit fly Drosophila melanogaster as a model system, which allows incisive molecular genetic analysis and physiological measurement of individual olfactory cells. The project addresses the molecular and cellular logic of odor coding through three specific aims. The first aim is to define the response spectrum and temporal dynamics of virtually the entire repertoire of antennal receptors with respect to a panel of 100 odorants in an in vivo expression system, and to determine whether the receptors can carry out simple logical operations. The aim is designed to address central questions about the mechanism of odor coding. The second aim is to map odor receptors to neurons, with the goal of testing the extent to which the one receptor-one neuron rule describes olfactory system organization. The third aim is to test the hypothesis that two members of the odor receptor gene family encode pheromone receptors that suppress mating behavior. Diseases carried by insects afflict hundreds of millions of people every year, and many of these insects locate their human hosts and their mates through olfactory cues. Advances in the understanding of olfactory and pheromonal reception could lead to new means of controlling these insect vectors of human disease.